AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
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DOI：
10.1038/35008115
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发表时间：
2000-04-13
期刊：
影响因子：
64.8
通讯作者：
Burgering, BMT
中科院分区：
文献类型：
--
作者：
Medema, RH;Kops, GJPL;Burgering, BMT
叉头转录因子AFX、FKHR和FKHR- l1是DAF-16的同源物，DAF-16是调节秀丽隐杆线虫寿命的叉头因子（1-3）。在这里，我们发现这些叉头转录因子的过表达导致多种细胞系的生长抑制，包括ras转化细胞系和缺乏肿瘤抑制因子PTEN的细胞系。AFX的表达在G期阻断细胞周期进程(1)，不依赖于功能性视网膜母细胞瘤蛋白（pRb），但依赖于细胞周期抑制剂p27（kip1）。事实上，AFX转录激活p27(kip1)，导致蛋白水平升高。我们得出结论，afx样蛋白参与细胞周期调节，这些蛋白的失活是致癌转化的重要步骤。
The Forkhead transcription factors AFX, FKHR and FKHR-L1 are orthologues of DAF-16, a Forkhead factor that regulates longevity in Caenorhabditis elegans(1-3). Here we show that overexpression of these Forkhead transcription factors causes growth suppression in a variety of cell lines, including a Ras-transformed cell line and a cell line lacking the tumour suppressor PTEN. Expression of AFX blocks cell-cycle progression at phase G(1), independent of functional retinoblastoma protein (pRb) but dependent on the cell-cycle inhibitor p27(kip1). Indeed, AFX transcriptionally activates p27(kip1), resulting in increased protein levels. We conclude that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation.